Regulation of insulin receptors is being studied in vivo using circulating mononuclear cells and in vitro using cultured diploid fibroblasts. Investigation of monocytes and fibroblasts suggest that cells from obese subjects have more receptors, reduced insulin affinity, increased insulin degradation and decreased down regulation. Insulin fibroblasts and from human erythrocytes. Characterization of insulin binding to solubilized insulin receptor preparations resulted in binding affinity, pH optimum and analog specificity data similar to those for the intact cells. The binding of an insulin-like growth factor, Multiplication Stimulating Activity (MSA), as well as insulin were measured in suspended human fibroblasts and in solubilized receptor preparations. Neither Sephadex G-200 chromatography, wheat germ lectin chromatography nor nondenaturing polyacrylamide gel electrophoresis (with 0.1% Triton) separated the two receptors, although characterization of the specificity of binding clearly predicts two separate binding sites.